Beta interferon is a 20 kDa cytokine that exhibits antiviral, antiproliferative and immunomodulatory effects on many cell types. Recombinant human beta interferon products have annual worldwide sales of $4 billion, primarily from their use to treat Multiple Sclerosis. Beta interferon has a short half-life in humans, which necessitates frequent dosing and may not optimize therapeutic benefits of the protein for patients. We proposed that longer acting beta interferon products may provide patients with superior therapeutic benefits, in addition to a more convenient dosing regimen. During our Phase I SBIR grant we identified sites in beta interferon that can be modified with polymers without affecting the protein's in vitro bioactivity. During the Phase II portion of our grant, we developed manufacturing processes to produce sufficient quantities of the modified beta interferon proteins for testing in animals. These studies demonstrated that our polymer-modified protein has a longer half-life than a leading commercial beta interferon product and is significantly more effective than the commercial beta interferon product in an animal disease model. The goals of this Phase II continuing renewal proposal are to manufacture the protein under GLP (Good Laboratory Practices) conditions and measure the safety profile and pharmacokinetic properties of the protein in animal pharmacology and toxicology studies, which are required by the FDA prior to testing the compound in humans. The improved characteristics of our novel beta interferon analog may provide Multiple Sclerosis patients with a more effective and more convenient therapy for treatment of their disease. In addition, this compound has the potential to reduce the amount of beta interferon required per patient, reduce toxicity, reduce immunogenicity and incidence of neutralizing antibodies, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. This long-acting beta interferon analog also may prove useful for the treatment of cancer and viral diseases such as hepatitis. PUBLIC HEALTH RELEVANCE: Recombinant beta interferon is used to treat patients with Multiple Sclerosis, which affects an estimated 400,000 people in the United States. Beta interferon typically is administered to patients by thrice weekly subcutaneous injection due to its short half-life in people. We created longer acting beta interferon analogs that are significantly more efficacious than a leading commercial beta interferon in animal disease models. The goals of this Phase II continuing renewal proposal are to manufacture the protein under GLP (Good Laboratory Practices) conditions and measure the safety profile and pharmacokinetic properties of the protein in animal pharmacology and toxicology studies, which are required by the FDA prior to testing the compound in humans. This protein may provide Multiple Sclerosis patients with a more effective and more convenient therapy for the treatment their disease. [unreadable] [unreadable] [unreadable]